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St. John’s wort as Effective as Popular Prescription Anti-Depressant New Trial Demonstrates Herb’s Benefit and Safety Compared to Paroxetine
A new clinical study shows that a proprietary standardized extract of St. John’s wort
(SJW) was as effective as a common prescription antidepressant drug in reducing symptoms of
depression. The study was published Friday, February 11 in the British Medical Journal.1
According to the randomized, double-blind, reference-controlled trial, patients who
took 900mg per day of a SJW extract known as WS® 5570 (W. Schwabe, Karlsruhe, Germany)
had as much benefit as the pharmaceutical drug paroxetine (Paxil®, GlaxoSmithKline).
Paroxetine is a prescription antidepressant drug in the class known as SSRI’s (selective
serotonin reuptake inhibitors). In some clinical outcomes, including the primary efficacy
endpoint (a decrease of the depression scale score), WS 5570 was superior to the
A reference-controlled trial is different than a placebo-controlled trial where some of
the patients take a placebo (a dose with no active ingredient) as a control to test the effect of the
herb or drug being studied. In a reference-controlled trial, the substance being tested is
compared directly to a known active material, in this case, the FDA-approved prescription
The trial took place in various centers in Germany on patients from the ages of 18 to 70
during the years 2000 to 2003. The full treatment period was for 6 weeks. The patients had been
diagnosed to have moderate to severe levels of major depression.
In the study, 251 patients were randomized to receive either 900 mg/day of WS 5570 or
20 mg/day of paroxetine. If a patient did not experience a measurable response after 2 weeks,
the dose was doubled. Patients in the SJW group experienced significantly better improvement
as measured by the Hamilton Depression Rating Scale (HAMD), an internationally accepted
The trial results showed that the SJW actually produced a better HAMD improvement
than the pharmaceutical drug; patients in the SJW group experienced a three-point greater
decrease in the average HAMD total score compared to the original scores (baseline) than did
those taking paroxetine. The improvement in the SJW patients was considered clinically
significant: there was a responder rate (50% improvement on HAMD) of 70% for the SJW
patients versus 60% for those on paroxetine and a remission rate (HAMD equal or less than 10)
of 50% for SJW versus 35% for paroxetine. Further, in the secondary efficacy measures (other
standard depression scales including the clinical global impression), SJW was rated
Regarding the safety aspects of the trial, the SJW produced significantly fewer adverse
side effects than the drug. The paroxetine patients reported 269 adverse effects compared to
only 172 for those on SJW. The most frequently reported adverse effect for both treatments was
stomach upset, a fairly common side effect in many clinical trials of this type.
“This trial can help resolve some of the confusion surrounding the potential benefits of
St. John’s wort,” said Mark Blumenthal, founder and executive director of the nonprofit
American Botanical Council. “Most of the clinical trials show that several types of St. John’s
wort extracts produce clinically measurable and significant benefits.”
The results of this trial are consistent with a previously published larger trial in France.
In that double-blind, randomized, placebo-controlled trial conducted on 375 subjects, 900 mg
per day of the same SJW extract (WS 5570) showed more benefit for depressed patients than
St. John’s wort (Hypericum perforatum) is a traditionally used herbal remedy for
“melancholy” and related depressive states. Numerous clinical trials have demonstrated the
overall effectiveness and safety of various SJW preparations. In 1996 the British Medical Journal published a meta-analysis of 23 previously published clinical trials on the hypericin-
standardized SJW extract (hypericin is one of the compounds in SJW) concluding that the SJW
was safe and effective in treating mild to moderate forms of major depression.3 A highly
publicized trial in 2002 funded by the National Center for Complementary and Alternative
Medicine of the National Institutes of Health concluded that a hypericin-standardized SJW
preparation and the popular prescription antidepressant drug sertraline (Zoloft®, Pfizer) were
ineffective in treating patients with chronic moderate to severe depression.4 A follow-up meta-
analysis confirms that SJW preparations are more effective than placebo in mild to moderate
A dietary supplement product of identical strength to WS® 5570 is available in health
food stores in the United States under the trade name Perika® (Nature’s Way Products,
Springville, UT). Marketed for helping to create a positive mood, this product (known as WS®
5572) contains the same patented, standardized extract as WS 5570. Both WS 5570 and WS
5572 are standardized to SJW’s hyperforin (another of the compounds in SJW) content at levels
of 3-5 percent. Most other clinical trials on SJW have utilized an SJW extract standardized to
0.3 percent levels of total hypericins (LI 1370 aka Jarsin 300, Lichtwer Pharma, Berlin,
SJW has recently received public attention because of its ability to interact with a
variety of pharmaceutical drugs, lowering their levels and effectiveness. Blumenthal noted,
“The American Botanical Council recommends that consumers who are taking conventional
drugs and who also might be considering using St. John’s wort should first consult with a
qualified healthcare practitioner to determine if the herb might interact with their drugs.”
References 1 Szegedi A, Kohnen R, Dienel A, Kieser M. Acute Treatment of Moderate to Severe Depression
with Hypericum Extract WS® 5570 (St. John’s Wort): Randomized, Controlled, Double-Blind,
Non-Inferiority Trial versus Peroxetine. British Medical Journal 2005, BMJ Online First.
2 Lecrubier Y, Clerc G, Didi R, Kieser M. Efficacy of St. John's Wort Extract WS® 5570 in
Major Depression: A Double-Blind, Placebo-Controlled Trial. American Journal of Psychiatry
3 Linde K, Ramirez G, Mulrow C, Pauls A, Weidenhammer W, Melchart D. St. John's wort for
depression—an overview and meta-analysis of randomized clinical trials. BMJ 1996;
4 Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St. John’s wort)
in major depressive disorder. JAMA 2002;287:1807-14.
5 Linde K, Mulrow CD. St John’s wort for depression. Cochrane Database Syst Rev

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